【摘要】：目的：探討天王復(fù)心方抗心肌缺血作用及其可能作用機(jī)理。 方法： 1.采用結(jié)扎大鼠冠狀動(dòng)脈法復(fù)制心肌缺血模型,連續(xù)給藥21天后,觀察各組動(dòng)物心電圖ST段的變化,心肌梗死面積、血清磷酸肌酸激酶(CK)、乳酸脫氫酶(LDH)含量及心肌組織勻漿液SOD、MDA含量。 2.采用異丙腎上腺素多次給藥法復(fù)制心肌缺血模型,觀察天王復(fù)心方對(duì)心肌缺血模型大鼠心肌損傷程度和損傷范圍的影響及血清肌酸磷酸激酶(CK)和乳酸脫氫酶(LDH)變化的影響。 3.以麻醉犬為研究對(duì)象,通過(guò)八道生理記錄儀,觀察了天王復(fù)心方對(duì)動(dòng)物血壓、心率、左室內(nèi)壓、左室內(nèi)壓變化速率、主動(dòng)脈血流量、冠狀動(dòng)脈血流量、總外周阻力、心肌耗氧量等指標(biāo)的影響。 4.采用注射腎上腺素與冰水刺激相結(jié)合的方法復(fù)制大鼠血瘀證模型,觀察天王復(fù)心方對(duì)血瘀證大鼠血液流變學(xué)的影響。 5.采用電刺激大鼠頸總動(dòng)脈血栓形成法,觀察不同劑量受試藥物對(duì)動(dòng)脈內(nèi)血栓形成(堵塞動(dòng)脈)時(shí)間(OT)的影響。 6.采用正常大鼠富含血小板的血漿,以5-腺苷二磷酸二鈉鹽(ADP)為促凝劑,通過(guò)血小板聚集儀測(cè)血小板聚集曲線,以血小板凝集1分鐘(PAGl)、5分鐘(PAG5)和最大峰值(PAGM)為觀測(cè)指標(biāo),比較給藥各組與空白對(duì)照組(生理鹽水)血小板聚集率。 7.用結(jié)扎大鼠冠狀動(dòng)脈法復(fù)制心肌缺血模型,連續(xù)給藥21天后,采用免疫組化和PCR法觀察TLR4-NFκB P65表達(dá)的影響 結(jié)果： 1.結(jié)果表明,天王復(fù)心方可明顯減輕心肌損傷的程度,縮小壞死區(qū)范圍,降低血漿磷酸肌酸激酶(CK)、乳酸脫氫酶(LDH)含量,提高心肌組織SOD活性,降低MDA含量。提示天王復(fù)心方對(duì)動(dòng)物心肌缺血所致的心肌損傷有保護(hù)作用。 2.結(jié)果表明,天王復(fù)心方對(duì)異丙腎腺素亞急性心肌缺血?jiǎng)游锏男募p傷有明顯的保護(hù)作用,可不同程度的的減輕心肌損傷程度,對(duì)心肌血清肌酸磷酸激素酶(CK)和乳酸脫氫酶(LDH)水平升高有一定的抑制作用。 3.結(jié)果表明,天王復(fù)心方高劑量和中劑量可輕度降低血壓,增加冠狀動(dòng)脈血流量和主動(dòng)脈流量,降低總外周阻力,降低心肌耗氧量,對(duì)心率沒(méi)有明顯的影響。 4.天王復(fù)心方對(duì)瘀血證大鼠不同切變率下的全血粘度升高有明顯的改善作用,對(duì)血漿粘度升高有一定改善作用。 5.天王復(fù)心方(2g·kg-1體重和1g·kg-1體重)給藥可明顯延長(zhǎng)電刺激大鼠頸總動(dòng)脈血栓形成時(shí)間(堵塞動(dòng)脈),表明天王復(fù)心方具有抑制血栓形成作用。 6.天王復(fù)心方體外100mg/ml和50mg/ml在1min、5min測(cè)試點(diǎn)上血小板聚集率明顯小于對(duì)照組,血小板聚集最大峰值明顯低于對(duì)照組,提示天王復(fù)心方體外給藥對(duì)ADP所致的血小板聚集均有明顯的抑制作用。 7.天王復(fù)心方對(duì)心肌缺血大鼠炎癥調(diào)控信號(hào)TLR4蛋白與基因、NFκB蛋白表達(dá)有抑制作用。 結(jié)論：天王復(fù)心方具有抗凝、抗血栓形成和抗心肌缺血作用,其機(jī)制可能與調(diào)節(jié)炎癥信號(hào)TLR4-NFκB有關(guān)。
[Abstract]:Objective: to investigate the anti-myocardial ischemia effect of Tianwang Fuxin decoction (FXF) and its possible mechanism. Methods: 1. Myocardial ischemia model was established by ligation of coronary artery in rats. After 21 days of continuous administration, the changes of ST segment, myocardial infarction area and serum creatine phosphokinase (CK), were observed in each group. (LDH) content of lactate dehydrogenase and SOD,MDA content of myocardial homogenate. 2. Myocardial ischemia model was established by multiple administration of isoproterenol. To observe the effect of Tianwang Fuxin recipe on myocardial injury degree and damage range and the changes of serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) (LDH) in rats with myocardial ischemia. 3. The changes of blood pressure, heart rate, left ventricular pressure, aortic blood flow, coronary artery blood flow and total peripheral resistance were observed in anesthetized dogs. The influence of myocardial oxygen consumption and other indexes. 4. The effect of Tianwang Fuxin recipe on hemorheology of rats with blood stasis syndrome was observed by the method of injection of epinephrine and ice water stimulation. 5. The effects of different doses of drugs on the time of thrombosis (clogging) time (OT) of common carotid artery in rats were studied by electrical stimulation. 6. Using platelet-rich plasma of normal rats and 5-adenosine diphosphate disodium salt (ADP) as coagulant, platelet aggregation curve was measured by platelet aggregator, and platelet agglutination was used for 1 minute (PAGl),. Five minutes (PAG5) and maximum peak (PAGM) were measured to compare the platelet aggregation rate between the administration group and the blank control group (normal saline). 7. Myocardial ischemia model was established by ligation of coronary artery in rats. After 21 days of continuous administration, the expression of TLR4-NF 魏 B p65 was observed by immunohistochemical and PCR methods: 1. The results showed that Tianwang Fuxin decoction could obviously reduce the degree of myocardial injury, reduce the area of necrosis, decrease the content of plasma creatine kinase (CK), lactate dehydrogenase (LDH), increase the activity of SOD and decrease the content of MDA. It suggests that Tianwang Fuxin recipe has protective effect on myocardial injury caused by myocardial ischemia. 2. The results showed that Tianwangfuxin recipe had obvious protective effect on myocardial injury of isopropanol subacute myocardial ischemia animals, and could alleviate myocardial injury degree in varying degrees. It can inhibit the increase of serum creatine phosphatase (CK) and lactate dehydrogenase (LDH) levels. 3. The results showed that the high and middle dose of Tianwang Fuxin recipe could decrease blood pressure, increase coronary blood flow and aortic flow, decrease total peripheral resistance and decrease myocardial oxygen consumption, but had no obvious effect on heart rate. 4. Tianwang Fuxin prescription can obviously improve the whole blood viscosity under different shear rates of blood stasis syndrome rats, and improve the plasma viscosity to some extent. 5. Tianwang Fuxin prescription (2 g kg-1 weight and 1 g kg-1 body weight) could significantly prolong the time of thrombosis formation (clogging artery) of rat common carotid artery stimulated by electrical stimulation, which indicated that Tianwang Fuxin prescription could inhibit thrombosis. 6. The platelet aggregation rate of 100mg/ml and 50mg/ml in vitro was significantly lower than that of the control group, and the peak value of platelet aggregation was significantly lower than that of the control group. The results suggest that Tianwang Fuxin prescription has obvious inhibitory effect on platelet aggregation induced by ADP in vitro. 7. Tianwang Fuxin recipe can inhibit the expression of TLR4 protein and gene, NF 魏 B protein of inflammatory regulation signal in myocardial ischemia rats. Conclusion: Tianwang Fuxin recipe has anticoagulant, antithrombotic and anti-myocardial ischemia effects, and its mechanism may be related to the regulation of inflammatory signal TLR4-NF 魏 B.
【學(xué)位授予單位】：湖南中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R285

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